The ubiquinol (which is also referred to as a reduced coenzyme Q10, a reduced CoQ10, and a reduced form coenzyme Q10) is a strong antioxidative component and is a functional substance widely used in supplements for preventing cardiac diseases and the like all over the world.
The utilization efficiency of the ubiquinol in the body is higher than that of ubiquinone (oxidized coenzyme Q10) which is an oxidation form of the ubiquinol. Therefore, a supplement of the ubiquinol is dealt with a high price nearly twice the price of a supplement of the ubiquinone. The ubiquinol, however, is likely to be oxidized to ubiquinone due to oxygen and the like in the air, and thus is a very unstable substance, which has made it difficult to stably blend the ubiquinol in a supplement.
Heretofore, some methods for stabilizing the ubiquinol are known (Patent Documents 1 to 6).
Patent Documents 1 to 3 describe methods for causing a surfactant (for example, emulsifier) to coexist in ubiquinol. However, when a large amount of the ubiquinol is blended in foods and cosmetics, it is necessary to increase the addition amount of an emulsifier in connection with the increase in the ubiquinol, which has great influence on the physical properties, the taste, and the cost of the foods and the cosmetics. Moreover, consumers highly interested in health and beauty tend to strongly prefer natural raw materials, and thus it is expected that the consumers do not prefer the use of food additives such as an emulsifier.
Patent Documents 4 and 5 describe a method for stabilizing ubiquinol by blending citric acid and ascorbic acid. However, it cannot be said that the stability of ubiquinol is sufficient in these inventions (For example, when ubiquinol and citric acid or ascorbic acid were mixed, and then the mixture was allowed to stand still in the air at 25° C. for 4 days, the weight ratio of ubiquinol/ubiquinone was smaller than 90/10.) and the inventions do not have an effect of uniformly dispersing ubiquinol in an aqueous solution, and therefore the inventions cannot be applied to a water dispersible supplement.
Patent Document 6 describes a particle-like composition in which an oil-based component containing ubiquinol is dispersed in a water-soluble diluent. Although the particle-like composition obtained by the above-described invention has high reduced retention and oral absorbability, an emulsification process by a high-pressure homogenizer and a drying process such as spray dry are required, so that special facilities and cost are required. Moreover, for one having high reduced retention in Examples, the use of an emulsifier is indispensable. Moreover, the invention described above requires performing drying until the recovery in a particle state can be achieved. Accordingly, the remaining moisture amount is usually preferably 30% by weight or less, more preferably 10% by weight or less, and most preferably 5% by weight or less of the particle weight after the recovery.
Moreover, the ubiquinol has low solubility in water and thus easily causes crystallization and separation in water. Therefore, it has been more difficult to blend the ubiquinol in a water dispersible supplement in a high proportion.
In general, it is said that a water insoluble functional substance has low absorbability into the body. For example, a supplement having high dispersibility in water in which the absorbability into the body is increased by water-solubilizing or emulsifying the water insoluble functional substance has drawn attention. Also with respect to the ubiquinol having low solubility in water, a development of a technique of stably blending the ubiquinol in the water dispersible supplement in a high proportion has been long awaited.
In particular, pharmaceutical compounds and functional components to be blended in pharmaceutical agents and supplements are mostly fat-soluble substances. However, when orally taken, the fat-soluble substances difficult to dissolve in digestive organs. Therefore, it is generally known that the fat-soluble substances have low absorbability into the body of humans (Non-patent Document 1). Accordingly, increasing the absorption efficiency of the useful fat-soluble substances is a useful means for increasing the bioavailability. Thus, a large number of techniques have been developed, e.g., a means of processing a fat-soluble substance into a stable emulsified state with an emulsifier (Patent Document 7), a means of increasing the absorption efficiency by the use of an emulsifier and oil in combination (Patent Document 8), a means of controlling the particle size to the optimal particle system, such as fine particle size, as in a nano-emulsion (Patent Document 9), and a means of increasing the absorption efficiency by a drug delivery system (hereinafter referred to as “DDS”) of liposome and the like, and further preventing inconvenient decomposition (Patent Document 10).
The ubiquinol (functional component which is also referred to as a reduced coenzyme Q10) which is a fat-soluble substance is an active coenzyme Q10 which acts in the living body and is blended in dietary supplements and widely sold in advanced nations, mainly in the United States, as a component effective for preventing and treating cardiac diseases. However, there is a report of a clinical test that the absorbability of the ubiquinol into the body is low particularly in oral intake, and only about several percentages of the intake amount is absorbed into blood and the ubiquinol is mostly discharged (Non-patent Document 2). In usual, a general dosage form of the fat-soluble substance supplement is encapsulating the fat-soluble substance in a soft capsule in terms of the stability of components, the storageability and portability of products, and the ease of oral intake. In particular, in order to improve the absorption efficiency even just a little, a technique of encapsulating ubiquinol emulsified with an emulsifier or the like in a soft capsule is also known (Patent Document 11).
In order to encapsulate the fat-soluble substance in a soft capsule, it is usually necessary to dissolve the fat-soluble substance in oils and fats, such as vegetable oils and fats, or make the fat-soluble substance turbid in the form of slurry. Moreover, it is necessary to add an emulsifier, such as lecithin or sucrose fatty acid ester, for the purpose of homogenization. In particular, advanced emulsification processing is required to increase the absorbability and it is necessary to use a large amount of a plurality of emulsifiers or perform advanced processing (Patent Document 12).
However, the internal volume of one soft capsule is limited, and therefore the blending amount is limited when a large amount of a fat-soluble substance is blended in a stable emulsified state. Moreover, when the required intake amount of the target fat-soluble substance is large, the number of soft capsules to be taken also increases, which is a heavy burden on a user. Therefore, in order to blend a large amount of the fat-soluble substance, it cannot be said that the demand is sufficiently satisfied by the dosage form of the soft capsule. In particular in the United States, the intake amount of the ubiquinol is large and a supplement which is recommended to take by 400 mg/day or more as a coenzyme Q10 also increases. In this case, the number of the supplements to be taken is large or one particle size is large, which makes it difficult for a user to drink the same and further the burden of a user when supplements of other functional components are taken together is immeasurable. Therefore, a dosage form which allows blending of the ubiquinol in a high concentration, a dosage form which is not difficult to take a large amount of the ubiquinol, and also a dosage which allows intake without water at any time and at any place have been demanded.
In supplements aiming at health maintenance and health improvement and prevention of diseases, it is ideal to avoid the use of emulsifiers, such as oils and fats and fatty acid esters, as much as possible but it is ironical that lipid and emulsifiers need to be simultaneously taken in in order to take the fat-soluble functional component. Moreover, there is a tendency that health-conscious consumers do not prefer the emulsifier which is one of the raw materials from the viewpoint of palatability. In actual, there are a large number of products indicating “fat free” and “emulsifier free” as a feature and the products are supported by a large number of consumers.
As described above, in order to improve the absorbability of the fat-soluble functional component, such as ubiquinol, into the body, it is usually necessary to dissolve the fat-soluble functional component in oils and fats and further to obtain the fat-soluble functional component in a stable emulsified state using an emulsifier, however, on the other hand, there are also consumer needs, such as “fat free” and “emulsifier free”. Therefore, it has been difficult to achieve all the demands of high absorbability of ubiquinol into the body and the palatability of products.